rs369571041

Variant names:

• chr3-194604391-C-A
• rs369571041
• NM_001011655.3:c.1072G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-194604391-C-A
• chr3-194604391-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001011655.3(TMEM44):​c.1072G>T​(p.Ala358Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000502 in 1,395,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A358P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: TMEM44 NM_001011655.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81
• Publications: 0 publications found

Genes affected

TMEM44 (HGNC:25120): (transmembrane protein 44) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC105374291 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0442352).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011655.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM44	NM_001011655.3	MANE Select	c.1072G>T	p.Ala358Ser	missense	Exon 9 of 10	NP_001011655.1	Q2T9K0-2
	TMEM44	NM_001166305.2		c.1213G>T	p.Ala405Ser	missense	Exon 10 of 11	NP_001159777.1	Q2T9K0-1
	TMEM44	NM_138399.5		c.1072G>T	p.Ala358Ser	missense	Exon 9 of 11	NP_612408.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM44	ENST00000347147.9	TSL:1 MANE Select	c.1072G>T	p.Ala358Ser	missense	Exon 9 of 10	ENSP00000333355.6	Q2T9K0-2
	TMEM44	ENST00000392432.6	TSL:1	c.1213G>T	p.Ala405Ser	missense	Exon 10 of 11	ENSP00000376227.2	Q2T9K0-1
	TMEM44	ENST00000473092.5	TSL:1	c.1072G>T	p.Ala358Ser	missense	Exon 9 of 11	ENSP00000418674.1	Q2T9K0-7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000502 AC: 7 AN: 1395504 Hom.: 0 Cov.: 33 AF XY: 0.00000436 AC XY: 3 AN XY: 687602

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24940

East Asian (EAS) AF: 0.00 AC: 0 AN: 35712

South Asian (SAS) AF: 0.00 AC: 0 AN: 79074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.00000558 AC: 6 AN: 1076110

Other (OTH) AF: 0.0000173 AC: 1 AN: 57810

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.0050
DANN	Benign	0.48
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
PhyloP100		-2.8
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.032
Sift	Benign	0.055	T
Sift4G	Benign	0.24	T
Polyphen		0.010	B
Vest4		0.20
MutPred		0.13		Loss of glycosylation at P410 (P = 0.0195)
MVP		0.014
MPC		0.082
ClinPred		0.065	T
GERP RS		-6.5
Varity_R		0.053
gMVP		0.14
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs369571041; hg19: chr3-194325120;